Umpolung Strategy for Arene C–H Etherification Leading to Functionalized Chromanes Enabled by I(III) N-Ligated Hypervalent Iodine Reagents

Abstract

The direct formation of aryl C–O bonds via the intramolecular dehydrogenative coupling of a C–H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C–H etherification via an umpoled alcohol cyclization mediated by an I(III) N-HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary and tertiary alcohols via a cascade cyclization-iodonium salt formation, the latter providing a versatile functional handle for downstream derivatization. Computational studies support initial formation of an umpoled O-intermediate via I(III) ligand exchange, followed by competitive direct and spirocyclization/1,2-shift pathways.

I(III)-Mediated Arene C-H Amination using (Hetero)Aryl Nucleophiles

“…[9][10][11][12] In recent years, our laboratory has developed the I(III) N-HVI reagent class (4), which possess datively bound Nheterocyclic ligands (Scheme 1B, inset). [13][14][15][16][17] These reagents are bench stable, can be accessed in a single step from commercial materials, and are compatible with a broad range of heterocyclic ligands. 18 Recent work from our group has demonstrated their utility in "heterocyclic group transfer" (HGT) reactions with olefins as a novel means of accessing complex N-alkyl pyridinium salts.…”